Hyolaryngeal kinematics and swallow patterning in normal and disordered swallowing

Hyoid and laryngeal movements contribute to laryngeal vestibule closure and upper esophageal sphincter (UES) opening for safe swallowing. However, the extent of movement required for achieving these goals, and the interaction between hyoid and laryngeal movements during swallowing are unknown. Despite impairment in vestibule closure and UES opening, patients with dysphagia may exhibit reduced, increased or similar hyolaryngeal displacements as healthy individuals. This limits the delineation between normal and disordered swallowing. We investigated whether anatomical differences in hyolaryngeal positions and the extent of laryngeal vestibule opening at rest would better predict hyolaryngeal displacements and the extent of vestibule closure during swallowing than neck length. We then examined if hyolaryngeal maximal displacements that corrected for individual anatomical differences would show greater contrast between the swallows of patients and healthy individuals than uncorrected measures. We also investigated if the relationship between hyoid and laryngeal elevation, as well as measures of laryngeal elevation peak velocity, timing and movement patterning would differ between patients and controls swallowing more than corresponding measures of hyoid elevation. Videofluoroscopic examinations of swallowing were performed in healthy adults and patients with dysphagia. Using frame-by-frame motion analysis, measures of forward and upward hyolaryngeal displacements and velocities, and vestibule area were made during swallowing. In healthy volunteers, the extent of laryngeal vestibule opening at rest predicted the extent to which laryngeal elevation exceeded hyoid elevation for closing the space between the hyoid and larynx during swallowing. Spatially normalized measures of hyoid and laryngeal elevation magnitudes showed greater differences between normal and abnormal swallowing than raw measures. Patients with dysphagia had insufficient laryngeal elevation relative to hyoid elevation to achieve vestibule closure during swallowing. In conclusion, healthy individuals may adapt hyolaryngeal movement magnitudes according to changes in the movement targets required for vestibule closure to ensure safe swallowing. Insufficient laryngeal elevation relative to hyoid elevation may be detrimental to airway protection for swallowing in dysphagia

Aqua­[N′-(3-eth­oxy-2-oxidobenzyl-κO)furan-1-carbohydrazidato-κ2 N′,O]dioxido­molybdenum(VI)–4,4′-bipyridine (2/1)

The MoVI atom in the title co-crystal, [Mo(C14H12N2O4)O2(H2O)]·0.5C10H8N2, is O,N,O′-chelated by the deprotonated Schiff base and coordinated by the oxide and water O atoms in an octa­hedral geometry. The five-membered chelate ring is planar (r.m.s. deviation = 0.019 Å), but the six-membered chelate ring is puckered (r.m.s. deviation = 0.108 Å). Two mononuclear mol­ecules are linked across a center of inversion by an O—Hwater⋯O hydrogen bond; adjacent dinuclear units are linked by an water–4,4′-bipyridine O—H⋯N hydrogen bond, generating a linear chain structure. The 4,4′-bipyridine mol­ecule is disordered over two positions in a 1:1 ratio

cis-(Dimethyl sulfoxide-κO)[N′-(3-eth­oxy-2-oxidobenzyl­idene-κO)-2-hy­droxy­benzohydrazidato-κ2 N′,O]dioxido­molybdenum(VI)

The coordination geometry at the MoVI atom in the title compound, [Mo(C16H14N2O4)O2(C2H6OS)], is distorted octa­hedral. The phenolate O, imino N, oxide O from the enolized carbonyl group and one of the terminal O atoms form the equatorial plane; the axial positions are occupied by the other terminal O atom of the dioxidomolybdenum group and the donor O atom of DMSO. The O=Mo=O angle is 105.31 (6)°. An intra­molecular O—H⋯N hydrogen bond and weak inter­molecular C—H⋯O hydrogen bonds are present in the structure

[N′-(5-Chloro-2-oxidobenzyl-κO)-2,4-dihy­droxy­benzohydrazidato-κ2 N′,O](methanol-κO)dioxidomolybdenum(VI)–4,4′-bipyridine (1/1)

In the title co-crystal, [Mo(C14H9ClN2O4)O2(CH3OH)]·C10H8N2, the deprotonated Schiff base O,N,O′-chelates to the MoVI atom, the three atoms involved in chelation comprising the fac sites of the octa­hedron surrounding the methanol-coordinated metal atom. The methanol mol­ecule forms an O—H⋯N hydrogen bond to an N atom of the 4,4′-bipyridine solvent mol­ecule; the hy­droxy group of the Schiff base forms an O—H⋯N hydrogen bond to the other N atom of another mol­ecule. The two hydrogen bonds leading to the formation of a helical chain running along the b axis

Predicting the catalytic sites of isopenicillin N synthase (IPNS) related non-haem iron-dependent oxygenases and oxidases (NHIDOX) through a structural superimposition and molecular docking approach

Isopenicillin N synthase (IPNS) related Non-haem iron-dependent oxygenases and oxidases (NHIDOX) demonstrated a striking structural conservativeness, even with low protein sequence homology. It is evident that these enzymes have an architecturally similar catalytic centre with active ligands lining the reactive pocket. Deacetoxycephalosporin C synthase (DAOCS), isopenicillin N synthase (IPNS), deacetylcephalosporin C synthase (DACS), clavaminate synthase 1 and 2 (CAS1 and 2) are important bacterial enzymes that catalyze the formation of β-lactam antibiotics belonging to this enzyme family. Most plant enzyme members within this subfamily namely flavonol synthase (FLS), leucoanthocyanidin dioxygenase (LDOX), anthocyanidin synthase (ANS), 1-aminocyclopropane-1-carboxylic acid oxidase (ACCO), gibberellin 20-oxidase (G20O), desacetoxyvindoline-4-hydroxylase (D4H), flavanone 3β-hydroxylase (F3H), and hyoscyamine 6β-hydroxylase (H6H) are involved in catalyzing the biosyntheses of plant secondary metabolites. With the advancement of protein structural analysis software, it is possible to predict the catalytic sites of protein that shared a structural resemblance. By exploiting the superimposition model of DAOCS-IPNS, DAOCS-IPNS-CAS, G20O-LDOX, FLS-LDOX, ACCO-LDOX, D4H-LDOX, F3H-LDOX and H6H-LDOX model; a computational protocol for predicting the catalytic sites of proteins is now made available. This study shows that without the crystallized or nuclear magnetic resonance (NMR) structures of most NHIDOX enzyme, the plausible catalytic sites of protein can be forecasted using this structural bioinformatics approach.Keywords: Enzyme, catalytic sites, isopenicillin N synthase, ligand

FOXO-regulated DEAF1 controls muscle regeneration through autophagy

The commonality between various muscle diseases is the loss of muscle mass, function, and regeneration, which severely restricts mobility and impairs the quality of life. With muscle stem cells (MuSCs) playing a key role in facilitating muscle repair, targeting regulators of muscle regeneration has been shown to be a promising therapeutic approach to repair muscles. However, the underlying molecular mechanisms driving muscle regeneration are complex and poorly understood. Here, we identified a new regulator of muscle regeneration, Deaf1 (Deformed epidermal autoregulatory factor-1) – a transcriptional factor downstream of foxo signaling. We showed that Deaf1 is transcriptionally repressed by FOXOs and that DEAF1 targets to Pik3c3 and Atg16l1 promoter regions and suppresses their expression. Deaf1 depletion therefore induces macroautophagy/autophagy, which in turn blocks MuSC survival and differentiation. In contrast, Deaf1 overexpression inactivates autophagy in MuSCs, leading to increased protein aggregation and cell death. The fact that Deaf1 depletion and its overexpression both lead to defects in muscle regeneration highlights the importance of fine tuning DEAF1-regulated autophagy during muscle regeneration. We further showed that Deaf1 expression is altered in aging and cachectic MuSCs. Manipulation of Deaf1 expression can attenuate muscle atrophy and restore muscle regeneration in aged mice or mice with cachectic cancers. Together, our findings unveil an evolutionarily conserved role for DEAF1 in muscle regeneration, providing insights into the development of new therapeutic strategies against muscle atrophy

Accounting for degerred tax

The area of corporate income taxation is one of the most controversial issues facing the accounting profession in Singapore as it is in many other parts of the world.ACCOUNTANC

Eating with a purpose: development and motivators for consumption of superfood

This research aimed to examine an integrated and modified Health Belief Model by encapsulating the factors influencing consumer likelihood to consume superfoods as adjusted to the Malaysian population. It was conducted in Peninsular Malaysia from May 2019 until October 2019 using a sample size of 1,000 individuals obtained via purposive sampling, whereby the data were analysed by using structural equation modelling. The result showed that consumer likelihood to consume superfoods was positively influenced by perceived benefits and perceived susceptibility, while negatively influenced by perceived barrier. The cue to action had a direct influence on perceived susceptibility, perceived seriousness, and perceived benefits. Surprisingly, the cue to action was not too influential on perceived barrier and likelihood to consume superfoods. Nevertheless, the proposed modified Health Belief Model fitted the data better than the original model. This implied that it is important to focus on the cue to action especially in the superfood-buying context as opposed to the original Health Belief Model which neglected the cue to action

Home-based vibratory stimulation for chronic severe dysphagia (Kamarunas et al., 2022)

Purpose: Previously, externally placed vibratory laryngeal stimulation increased rates of swallowing in persons with and without dysphagia. This study examined the feasibility of using a vibratory device on the skin over the thyroid cartilage for home-based swallowing rehabilitation in long-standing dysphagia. Method: Only participants with long-standing dysphagia (> 6 months) following cerebrovascular accident or head/neck cancer who had not previously benefited from dysphagia therapy participated. The device had two modes used daily for 90 days. In automatic mode, participants wore the device when awake, which vibrated for 4–8 s every 5 min to trigger a volitional swallow. In manual mode, participants practiced by activating vibration while swallowing rapidly. Study-related adverse events, such as pneumonia, and device-recorded adherence were tracked. Swallowing function on a modified barium swallow study was assessed at baseline and after 3 months of device use. Outcome measures included the Dysphagia Outcome and Severity Scale (DOSS), Penetration–Aspiration Scale (PAS), and swallowing timing measures. Participants’ perceptions of the vibratory device and training were obtained. Results: The intent to treat analysis showed seven of 11 participants completed the study, all with severe chronic dysphagia. Of those seven participants completing the study, two developed respiratory complications (possibly due to pneumonia) that cleared after antibiotic intervention. For prescribed practice trials, adherence was 80% or greater in four of seven participants (57%) whereas prescribed automatic stimulations were met in only two of seven participants (29%). Three participants (43%) had a modest benefit on DOSS. The time to vestibule closure after the bolus passed the ramus was reduced in five participants (71%) on the modified barium swallow study. Conclusion: Overall, the results have indicated that intensive home-based practice with stimulation may provide limited functional benefits in severe chronic dysphagia. Supplemental Material S1. Participant survey on usability of device. Kamarunas, E., Mulheren, R., Wong, S. M., Griffin, L., & Ludlow, C. L. (2022). The feasibility of home-based treatment using vibratory stimulation in chronic severe dysphagia. American Journal of Speech-Language Pathology. Advance online publication. https://doi.org/10.1044/2022_AJSLP-22-00045</p